Neopterin is a biomarker of the activation of cellular immunity. The purpose of this review is to summarise neopterin metabolism, methods of its detection, and its role in inflammation, focusing on periodontal inflammatory diseases. This derivative of guanosine is a non-enzymatic product of 7,8-dihydroneopterin oxidation caused by free radicals which protect activated macrophages from oxidative stress. Various methods, usually based on enzyme-linked immunosorbent essay, high-performance liquid chromatography, or radioimmunoassay were developed for the isolation of neopterin. A wide spectrum of diseases and conditions are known to affect neopterin levels, including cardiovascular, bacterial, viral, and degenerative diseases, as well as malignant tumours. Neopterin levels were found to increase in subjects with periodontitis, especially when the oral fluid and gingival crevicular fluid were evaluated. These findings confirm the role of activated macrophages and cellular immunity in periodontal inflammatory diseases. The gingival crevicular fluid and the oral fluid appear to be the most valuable biologic fluids for the evaluation of neopterin levels in periodontitis. For gingival crevicular fluid, neopterin can be determined as the concentration or the so-called total amount. Nonsurgical periodontal treatment was associated with a decrease in neopterin levels, but an increase was also reported, suggesting the possible role of macrophages in the resolution of the periodontal lesion.

• Klíčová slova
• cellular immunity, inflammation, macrophages, neopterin, periodontitis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: At present, there are no strong predictors, nor a useful scoring system, that clearly identifies patients at risk for anastomotic leakage. AIM: This study aimed to investigate a new method that assesses this risk by monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids. MATERIAL AND METHODS: This prospective study included patients who underwent elective rectal resection for carcinoma. The basic condition for inclusion was rectal anastomosis using the double-stapling technique. Preoperative levels of neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and urine samples. These levels were then monitored for 6 postoperative days in venous blood, urine, and abdominal drainage fluid. RESULTS: A total of 42 patients were enrolled in the study. Thirty-six patients underwent a laparoscopic resection and 6 patients had an open procedure. No differences were found among neopterin, tryptophan, and kynurenine serum levels. However, the groups were observed to have significant differences in the urinary neopterin/creatinine ratio: the preoperative neopterin/creatinine ratio was 139.5 μmol/mol in the group with leakage, vs 114.8 μmol/mol in the group without complications, p = 0.037. The same results were observed during the postoperative period, p = 0.012. Additionally, the group with complications had a higher mean value of neopterin in drainage fluid, p = 0.048. CONCLUSIONS: Our study demonstrated that high preoperative levels of urinary neopterin could be interpreted as a risk for anastomotic leakage. Moreover, pathological levels of neopterin in urine and abdominal drainage fluid could be useful for early identification of anastomotic leakage during the postoperative period prior to its clinical development.

• Klíčová slova
• anastomotic leak, kynurenine, neopterin, rectal carcinoma, tryptophan,
• Publikační typ
• časopisecké články MeSH

With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine. Increased urinary or serum concentrations of neopterin have been associated with poor prognosis across a spectrum of malignant disorders of different primary location. Neopterin concentration in peripheral blood as well as in the tumor microenvironment correlates with phenotypic and functional changes of lymphocytes, indicating immune dysfunction. Increased neopterin concentrations are also accompanied by increased rate of conversion of tryptophan to kynurenine. Increasing neopterin concentrations also accompany side effects of anticancer treatment and could predict subsequent complications. Although almost four decades have elapsed since the discovery of increased neopterin concentrations in cancer patients, the full potential of neopterin as a biomarker in this setting has not been so far realized.

• Klíčová slova
• Kynurenine, neopterin, tryptophan,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment. Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol.

• MeSH
• adenokarcinom farmakoterapie   imunologie   metabolismus   radioterapie   MeSH
• alfa-tokoferol krev   MeSH
• antioxidancia metabolismus   MeSH
• chromatografie plynová MeSH
• dietní sacharidy farmakokinetika   MeSH
• diterpeny MeSH
• fluoruracil škodlivé účinky   terapeutické užití   MeSH
• intestinální absorpce * účinky léků   účinky záření   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory rekta farmakoterapie   imunologie   metabolismus   radioterapie   MeSH
• neopterin moč   MeSH
• protinádorové antimetabolity škodlivé účinky   terapeutické užití   MeSH
• retinylestery MeSH
• sacharidy moč   MeSH
• senioři MeSH
• vitamin A aplikace a dávkování   analogy a deriváty   krev   farmakokinetika   MeSH
• vysokoenergetická radioterapie škodlivé účinky   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa-tokoferol MeSH
• antioxidancia MeSH
• dietní sacharidy MeSH
• diterpeny MeSH
• fluoruracil MeSH
• neopterin MeSH
• protinádorové antimetabolity MeSH
• retinol palmitate MeSH Prohlížeč
• retinylestery MeSH
• sacharidy MeSH
• vitamin A MeSH